Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats

Schizophrenic patients suffer from deficits in information processing. Pati ents show both a decrease in P50 gating [assessed in the conditioning-testi ng (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substra te. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these i nformation processing paradigms in animals in order to investigate the effe cts of neurotransmitter manipulations in the brain. In order to validate th e animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/ kg, IP) was administered. Gating of an AEP component was changed due to inj ection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, IP) was investigated to assess its e ffects in the two gating paradigms. It was found that ketamine (10 mg/kg) d id not affect gating as measured with components of the AEP However, ketami ne (10 mg/kg) disrupted PPI of the startle response to the extent that prep ulse facilitation occurred. Firstly, it is concluded that AEP gating was di srupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T par adigm reflect distinct inhibitory sensory processes, since both paradigms a re differentially influenced by ketamine.